Mouse hepatitis virus (MHV) is a ubiquitous laboratory mouse coronavirus that has a number of potential and real effects on the research usefulness of infected mice. Much of the work on MHV has been derived using artificial routes of inoculation, microbiologically undefined mice and emphasis on only a few target organs. The overall objective of this work is to study the biology of this important mouse pathogen following a natural route of inoculation in microbiologically defined mice, so that its true significance can be assessed and its epizootiology understood. Studies will examine the infectivity of human coronavirus and rat coronaviruses for infant mice to determine if these closely related viruses are a source of natural infection in mouse colonies. Other studies will determine the duration of respiratory NHV infection and the mechanisms of virus entry, dissemination an excretion in susceptible mice. The pathogenesis of enterotropic MHV will also be examined in susceptible and resistant mouse genotypes. These studies will use virus titration, histology, immunohistochemistry and serology as markers of infection. The duration and effectiveness of the immune response to MHV will be studied. Data accumulated so far demonstrate that MHV infection has profound effects both on macrophage and lymphocyte function. Experiments will reveal whether suppression of mitogen-stimulated lymphocyte proliferation extends to other commonly used immunologic assays (e.g., MLR, CTL and PFC responses). Experiments are designed to address the mechanism of immunosuppression (direct virus effects, defective antigen presentation or altered interleukin production or receptor expression). Lastly, the factor produced by immunecells from infected mice that inhibits control cell responses will be characterized using biochemical and immunochemical methods. Data derived from this research project will have direct and immediate implications for understanding and managing this virus in laboratory mouse populations.